During its first five years, the Children's Environmental Health Center (CEHC) supported investigations of the roles of the environment and susceptibility in children's respiratory health. Important contributions were made supporting the growing consensus that current levels of ambient air pollutants and tobacco smoke have substantial adverse effects on children's respiratory health, especially among susceptible groups. The overall scientific and translational theme of the CEHC renewal application is air pollution, susceptibility, and childhood airway disease. The objectives proposed for the Center's next five years are: 1) to investigate the role of ambient air pollutants and genetic susceptibility in airway inflammation and in asthma occurrence during childhood; 2) to investigate the mechanism for the modulating effects of ambient air pollutants on allergic inflammation in children; 3) to implement a community-based participatory research program to respond to community concerns about the effects of regional ambient air pollutants and locally emitted fresh vehicle exhaust on early life asthma; 4) to provide a scientific resource for the broader community involved in protecting children's environmental health. In this application, the CEHC offers an innovative program of community-based participatory research, mechanistic and epidemiologic research to fill some pressing research and public health needs. The investigators propose a vigorous outreach and translation effort to ensure that communities, legislators, regulatory agencies, and other groups interested in children's environmental health are well informed about the evolving science and health impacts on children and communities. The proposed research program is integrated scientifically by a biological model that hypothesizes that chronic oxidative and nitrosative stress mediate the chronic effects of air pollution on asthma and allergic rhinitis. The investigators have identified six key research and translation questions about the adverse effects of ambient air pollution on children's airway diseases: 1) Do regional ambient air pollutants such as 03 or locally emitted fresh vehicle exhaust increase the risk of early life asthma? 2) Is chronic airway inflammation a risk factor for new onset asthma? 3) Do ambient air pollutants or locally emitted fresh vehicle exhaust produce chronic airway inflammation? 4) Do levels of expression or polymorphic variants of genes in antioxidant pathways such as GSTM1 confer special airway sensitivity to air pollution? 5) Which pollutants are responsible for the effects we see? 6) Can scientific approaches and translation to the broader community involved in protecting children's environmental health be enhanced by community-based participatory research approaches? Because the burden of airway disease and the numbers of children exposed to unhealthful air are large and growing, answers to these questions are urgently needed. The CEHC research program offers a timely opportunity to efficiently answer these key questions using an integrated approach and unique population and exposure assessment resources. Our collaborative multidisciplinary investigative team and strong working relationships with the community research partners, enhance the CEHC's ability to continue to contribute to understanding the effects of environmental exposures on childhood airway disease and to strengthen public health efforts to protect children.